The cornea depends on a high degree of cellular differentiation to fulfill its unique functions as an optically clear barrier and refractive surface at the front of the eye. The deceptively simple overall structure of the corneal epithelium, stroma, and endothelium is ultimately dictated by the spatial and temporal regulation of gene expression in these cells. The molecular events that control phenotypic expression in the layers of the cornea are very poorly understood; we have therefore undertaken to isolate and characterize cDNAs that are preferentially (and perhaps uniquely) expressed in the corneal epithelium and endothelium, using subtractive hybridization and subsequent differential screening.